2-(5-乙基-3,4-二苯基-吡唑-1-基)-联苯-3-基氧基]乙酸 | 300657-03-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(5-乙基-3,4-二苯基-吡唑-1-基)-联苯-3-基氧基]乙酸
• 中文别名: 2-[[2'-(5-乙基-3,4-二苯基-1H-吡唑-1-基)[1,1'-联苯]-3-基]氧基]乙酸
• 英文名称: BMS-309403
• 英文别名: 2-((2’-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)-[1,1‘-biphenyl]-3-yl)oxy)acetic acid；2-((2'-(5-Ethyl-3,4-diphenyl-1H-pyrazol-1-yl)-[1,1'-biphenyl]-3-yl)oxy)acetic acid；2-[3-[2-(5-ethyl-3,4-diphenylpyrazol-1-yl)phenyl]phenoxy]acetic acid
• CAS: 300657-03-8
• 化学式: C₃₁H₂₆N₂O₃
• 分子量: 474.559
• InChiKey: SJRVJRYZAQYCEE-UHFFFAOYSA-N

物化性质

• 沸点：
  657.5±55.0 °C(Predicted)
• 密度：
  1.17
• 溶解度：
  可溶于 DMSO（高达至少 25 mg/ml）。

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

BMS309403是FABP4的小分子抑制剂，其Kd值为4 nM，并且对FABP4的选择性远高于对FABP5和FABP3的100倍以上。

靶点

Target	Value
FABP4 (Cell-free assay)	4 nM(Kd)

体外研究

BMS-309403以剂量和时间依赖性的方式显著减少了THP-1巨噬细胞中MCP-1的产生。

体内研究

BMS-309403钠盐（每天给药，持续6周，剂量为15 mg/kg）在ApoE^−/−小鼠模型中表现出改善内皮功能、增加磷酸化和总型eNOS以及降低血浆甘油三酯水平的效果。但并未影响内皮依赖性松弛。

动物模型	C57BL/6J小鼠 (ApoE−/− 小鼠)
剂量	15 mg/kg
给药方式	持续治疗；每天6周
结果	显著增加了18周龄ApoE−/−小鼠主动脉中的磷酸化eNOS（Ser1177）和总型eNOS，但未改变磷酸化与总型eNOS的比例。

反应信息

• 作为产物：
  描述：

  Ethyl 2-[3-[2-(5-ethyl-3,4-diphenylpyrazol-1-yl)phenyl]phenoxy]acetate 在 sodium hydroxide 作用下， 以88%的产率得到2-(5-乙基-3,4-二苯基-吡唑-1-基)-联苯-3-基氧基]乙酸
  参考文献：
  名称：

  Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP)

  摘要：

  Herein we report the first disclosure of biphenyl azoles that are nanomolar binders of adipocyte fatty acid binding protein (aFABP or aP2) with up to thousand-fold selectivity against muscle fatty acid binding protein and epidermal fatty acid binding protein. In addition a new radio-ligand to determine binding against the three fatty acid binding proteins was also synthesized. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.044

文献信息

• Novel phenyl-substituted imidazolidines, process for preparation thereof, medicaments comprising said compounds and use thereof
  申请人：JAEHNE Gerhard

  公开号：US20110178134A1

  公开（公告）日：2011-07-21

  The invention relates to compounds of formula (I) wherein the groups have stated meanings, and to their physiologically compatible salts. Said compounds are suitable, for example, as anti-obesity drugs and for treating cardiometabolic syndrome.

  本发明涉及具有所述意义的公式（I）的化合物，以及它们的生理相容性盐。所述化合物适用于例如作为抗肥胖药物和治疗心血管代谢综合征。
• AZOLOPYRIDIN-3-ONE DERIVATIVES AS INHIBITORS OF LIPASES AND PHOSPHOLIPASES
  申请人：Petry Stefan

  公开号：US20130157941A1

  公开（公告）日：2013-06-20

  The present invention relates to azolopyridin-3-one derivatives of the general formula (I) with the meanings specified in the description, to their pharmaceutically usable salts and to their use as drug substances.

  本发明涉及通式（I）所示的咪唑吡啶-3-酮衍生物，其含义如描述中所指定的，以及它们的药用盐和作为药物物质的用途。
• Arylchalcogenoarylalkyl-substituted imidazolidine-2,4-diones, process for preparation thereof, medicaments comprising these compounds and use thereof
  申请人：JAEHNE Gerhard

  公开号：US20110053947A1

  公开（公告）日：2011-03-03

  The invention relates to compounds of formula (I) wherein the groups R and R′, A, D, E, G, L, p and R1 to R10 have the stated meanings and to their physiologically compatible salts. Said compounds are suitable, for example, as anti-obesity drugs.

  本发明涉及具有公式（I）的化合物，其中R和R'、A、D、E、G、L、p以及R1至R10具有所述含义，以及它们的生理相容性盐。所述化合物例如可作为抗肥胖药物使用。
• Novel aromatic fluoroglycoside derivatives, pharmaceuticals comprising said compounds and the use thereof
  申请人：FRICK Wendelin

  公开号：US20110059910A1

  公开（公告）日：2011-03-10

  The invention relates to substituted aromatic fluoroglycoside derivatives, and to the physiologically compatible salts and physiologically functional derivatives thereof. The invention also relates to methods of lowering blood sugar and the treatment of type I and type II diabetes.

  这项发明涉及取代芳香族氟糖苷衍生物，以及其生理兼容盐和生理功能衍生物。该发明还涉及降低血糖和治疗I型和II型糖尿病的方法。
• HETEROCYCLICALLY SUBSTITUTED METHOXYPHENYL DERIVATIVES WITH AN OXO GROUP, PROCESSES FOR PREPARATION THEREOF AND USE THEREOF AS MEDICAMENTS
  申请人：KEIL Stefanie

  公开号：US20120004165A1

  公开（公告）日：2012-01-05

  Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments The invention relates to heterocyclically substituted methoxyphenyl derivatives with an oxo group, and to physiologically compatible salts thereof. The invention relates to compounds of the formula I in which R1, R2, R3, R4, R10, X, n, B 1 , B 2 , B 3 and B 4 are each defined as specified, and to the physiologically compatible salts thereof. The compounds are suitable, for example, for treatment of diabetes.

  含有氧代基的杂环取代甲氧基苯基衍生物，其制备方法及用途作为药物。该发明涉及含有氧代基的杂环取代甲氧基苯基衍生物，以及其生理兼容盐。该发明涉及以下式I的化合物 其中R1、R2、R3、R4、R10、X、n、B1、B2、B3和B4分别如规定所定义，以及其生理兼容盐。这些化合物适用于例如糖尿病的治疗。